Polycystic kidney disease (PKD) is a common genetic disease that is characterized by the development of fluid filled cysts in the kidney and is associated with high morbidity and mortality. Autosomal dominant PKD (ADPKD) affects approximately 1:1000 individuals, whereas autosomal recessive PKD (ARPKD) is seen in approximately 1:20,000 live births. The molecular mechanisms underlying cyst formation remain unclear. The recent work from the Director's laboratory has shown that polycystin-1 and -2 function as a receptor channel complex that mediates G protein and calcium signaling and mechanosensation. The director has developed a number of mouse models with mutations in the mouse ortholog of the human ADPKD gene and generated cell lines from these mouse mutants and their wild type littermates. Taking advantage of these and other reagents developed in the Director's laboratory, the Center investigators will explore the molecular mechanisms underling human polycystic kidney disease. Project 1 (Dr. Denker) will use biochemical, cell biological and genetic approaches to understand the role of heterotrimeric G proteins in PKD. In Project 2 Dr. Kreidberg will use a combination of cell and molecular bioiogical approaches to understand the role of cadherins and integrins in the pathogenesis of polycystic kidney disease. In Project 3 Dr. Zhou will use biochemical and cell biological approaches to understand the role of fibrocystin/polyductin (FPC) in comparison with the roles of polycystins in PKD;In Pilot and Feasibility Project 1 Dr. Vassilev will use electrophysiological approaches to study the regulation of the polycystin channel;In Pilot and Feasibility Project 2 Dr. Bonventre will use a combination of cell biological and genetic approaches to study the role of kidney injury molecule-1 and epithelial to mesenchyme transition in PKD. Each of these projects will be supported by a Core facility that will provide most up to date support on molecular imaging and an administrative Core.